1. Field of the Invention
This invention relates to new antitumor antibiotic substances and to their production and use.
2. Description of the Prior Art
U.K. Patent Application No. 2,141,425A discloses fermentation of certain strains of Actinomadura verrucosospora to produce an antitumor antibiotic complex designated BBM-1675 (later called esperamicin). This complex may be separated into two major bioactive components, BBM-1675 A.sub.1 and A.sub.2 (also called esperamicin A.sub.1 and A.sub.2) and four minor components designated BBM-1675 A.sub.3, A.sub.4, B.sub.1 and B.sub.2. Structures for the esperamicins were not provided in the U.K. reference.
U.S. patent application Ser. No. 770,335 filed Aug. 27, 1985 discloses antitumor antibiotic substances designated BBM-1675C and BBM-1675D produced by selective chemical hydrolysis of esperamicin A.sub.1 and A.sub.2.
U.S. Pat. No. 4,530,835 discloses fermentation of Streptomyces sp. ATCC 39363 to produce the antitumor antibiotics designated CL-1577A and B of unknown structure. Applicant believes that CL-1577A and B are identical to BBM-1675 A.sub.1 and A.sub.2.
U.S. Pat. No. 4,578,271 discloses fermentation of Actinomadura pulveraceus sp. nov. No. 6049, ATCC 39100, to produce the antitumor antibiotics WS 6049-A and -B of unknown structure. A culture of this organism has been deposited by applicant in the American Type Culture Collection, Rockville, Md., and added to its permanent collection of microorganisms as ATCC 53610.
Applicant's colleagues have isolated an antitumor antibiotic designated BBM-1675 A.sub.1b (esperamicin A.sub.1b) from the Actinomadura verrucosospora strain H964-62, ATCC 39334, culture disclosed in U.K. Patent Application No. 2,141,425A which they believe is identical with WS 6049-A disclosed in U.S. Pat. No. 4,578,271 (see J. Antibiotics 38 (11), 1605-1609, 1985).
Subsequent to the publication of the above-described references, applicant and his colleagues have determined the structure of esperamicins A.sub.1, A.sub.2 and A.sub.1b. These structures are indicated below. ##STR3##
______________________________________ Compound R.sup.1 R.sup.2 R.sup.3 ______________________________________ esperamicin A.sub.1 H AC CH(CH.sub.3).sub.2 esperamicin A.sub.2 AC H CH(CH.sub.3).sub.2 esperamicin A.sub.1b H AC CH.sub.2 CH.sub.3 ______________________________________ ##STR4##